Time for an update

On behalf of all of us at Cybin, I’d like to express our sincere gratitude to all of our shareholders for your ongoing support of our mission and the work that we do. We have made remarkable progress in the past year, as we pioneer potentially life-changing therapies that address multiple mental health disorders.?

Mental health disorders impact almost 1 billion people around the world and that number, unfortunately, is growing. One in 5 of us will experience a mental health disorder this year, with one in 2 of us having a mental health issue at some point in our lifetime. This means that every one of us knows someone affected by a mental health condition.?

In the U.S., a staggering 40 million people are taking SSRIs – treatments that are known to be ineffective for the majority of patients, with chronic daily side effects that often require additional treatment. For the past 40 years we have been treating the signs and symptoms of these disorders but, in the very near future, we may actually, for the first time, be able to change the course of these diseases and provide lasting remission for many patients.

With plans to initiate our Phase 3 pivotal program in late summer of 2024, we believe that we are on the cusp of breakthroughs that have the potential to redefine standards of care for the millions of sufferers around the world.?

These next few months in particular are shaping up to be an exciting and transformational period for us, as we anticipate sharing our 12-month Phase 2 efficacy data for CYB003 in depression and initiating our Phase 3 pivotal program, later followed by Phase 2 topline safety and efficacy data for CYB004 around year end or early Q1 2025.

Quite simply, in our sector, the race to complete Phase 3 is on, and I’m proud to say that Cybin – once considered an underdog – is now taking a top-tier position among peers.

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CYB003

Let’s talk about our lead program, CYB003, a proprietary deuterated psilocin molecule in development for the adjunctive treatment of Major Depressive Disorder, or MDD. Our Phase 2 study delivered the most impressive remission rates in the sector, with 75% of MDD patients still in remission at four months after just two doses of CYB003. ?We believe these to be truly remarkable results when compared to the current standard of care. Moving from Phase 2 to a Phase 3 program is where things get really exciting, as we move from theory to practice.

In August, we had a Type B Initial Breakthrough Therapy Meeting with the U.S. Food and Drug Administration in Washington, D.C. Following this productive meeting, we expect to commence our Phase 3 pivotal program in late summer. We have selected 30 clinical sites across the United States and Europe, based on two key criteria – (1) prior experience running psychedelic clinical trials and (2) having a controlled substance license in place – with the aim of accelerating site initiation and recruiting.

Recent headlines regarding the CRL received by Lykos for its MDMA product candidate have generated questions about the future of other psychoactive drugs. This?was a big moment for our sector, with all eyes watching in the aftermath of the FDA’s decision. That said, with our strong Phase 2 data, FDA support through Breakthrough Therapy Designation, and a clear regulatory road map, we remain confident as we enter this next phase of investigation.

Our Phase 3 pivotal program design, which is based on dialogue and aligned with the FDA, will implement multiple measures to attempt to mitigate the risk of functional unblinding. Our program will include a study with a three-arm design with a high dose, mid-dose, and placebo arm. Patients will not know if they received the therapeutic high dose or the sub-therapeutic mid-dose, thus mitigating the unblinding to an extent and addressing potential expectancy bias. The study will also use remote, independent, blinded raters who will not have any information on the dose received or the participant’s dosing experience. Further, the reporting of effects during the dosing session will be firewalled to ensure that the study team stays blinded.?

Our intention is to recruit participants who are largely psychedelic na?ve to reduce the impact of expectancy bias. The studies will assess long-term efficacy, with data points up to one year, to outlast any potential expectancy effects. And finally, the study will include manual and real time artificial intelligence screening of monitoring sessions to ensure monitor fidelity and patient safety.?

With the combination of these studies, we expect to collect efficacy data that will provide a picture of relapse rates, time to redosing and other factors.

We are eager to initiate this next phase of clinical development and to build on the positive impact of CYB003 to date, including rapid onset, short duration of effect, and importantly, durability of response & remission rates.

Importantly for CYB003, we expect to report 12-month efficacy data from the Phase 2 MDD study in the fourth quarter of this year.?Think about that – we will see what portion of patients are still responding to treatment 12 months after just two doses of CYB003.?

We believe there is potential for a paradigm shift in the way we treat depression – at a time when more effective treatment options are so desperately needed.

These encouraging findings, together with the granting of Breakthrough Therapy Designation by the FDA, reinforce our enthusiasm for the first ever adjunctive Phase 3 deuterated psilocybin analog?program globally. We hope that a rigorous?Phase 3 program will ultimately lead to regulatory approval and commercial launch.

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CYB004

Turning now to CYB004, our proprietary deuterated dimethyltryptamine program in development for the treatment of Generalized Anxiety Disorder, or GAD, where there is a massive unmet need. GAD is a life-threatening condition which we believe has the potential for Breakthrough Therapy status. With anxiety disorders affecting some 18%-19% of the population, this is the largest population of any mental health condition. We believe current treatments are inadequate, as 50% of patients with GAD do not respond to first line treatment with antidepressants such as SSRIs and SNRIs. Furthermore, 57% of patients with anxiety diagnoses do not adhere to antidepressant treatment after six months.

Currently, we are progressing our Phase 2 study of CYB004, and dosing is underway in a 36-patient study. CYB004 is a short-duration treatment from a single intramuscular administration, and we believe has the potential to provide rapid and sustained benefits. We expect to share topline safety and efficacy data around year-end, or early Q1 2025.

We are very excited about demonstrating proof-of-concept data for both of these programs. With our DMT program fast following our CYB003 program, we believe we are differentiating ourselves from our peers and establishing a leadership position.?

Looking ahead, we are also exploring potential future opportunities for our diverse portfolio in targeting additional neuropsychiatry indications with high unmet need, potentially affecting over 100 million people in the US alone.

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IP and expanded R&D leadership

Two other efforts I’ll touch on here are: (1) our focus on strengthening our intellectual property portfolio and (2) broadening our clinical leadership team as we enter this next, critical phase of our evolution as a drug development company.

With regard to IP, our patent portfolio now includes more than 70 granted patents and over 220 pending applications. I can’t overstate the importance of robust patent protection as we continue along the pathway to regulatory approvals.

We have also expanded our R&D team with the addition of two highly experienced drug development leaders -- Dr. Atul R. Mahableshwarkar, who is leading the CYB003 program; and Dr. Tom Macek, who is leading the CYB004 program. Both individuals bring a wealth of big pharma and CNS experience, including overseeing large, complex, global Phase 3 trials, that we expect will benefit our programs at this pivotal time.

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Increased Visibility

One of the items that shareholders were asked to vote on yesterday was authority for the company to institute a share consolidation. We sought this authorization in order to enable new institutional, fund & wealth managers and broad-based and targeted indices to participate in Cybin stock ownership.?At present, these groups are prevented from buying shares due to internal limitations related exclusively to share price.

As we continue to chip away at some of the stigma attached to psychedelic-based treatments, it is heartening that companies like Cybin are now a legitimate, longer play for investors, and we aim to appeal to as many new investors as possible.

When you consider the staggering number of people who face one or more of these often-devastating disorders – with more than 300 million people worldwide suffering from depression, alone – it is clear why the need for improved therapeutic options is so dire.?

Culturally today, there is more understanding and acceptance of the potential benefits of psychedelic-based treatments, and the political and regulatory landscapes are more supportive as well.

Our team is working tirelessly to progress our two most advanced programs – CYB003 and CYB004 – while also investigating other indications beyond MDD and GAD.?

These are new boundaries we are pushing, and we believe we have the rigor and the scientific knowledge to be first-to-market with truly innovative improvements to the current treatment landscape.

It is clear to us now that although the science and efficacy of psychedelic compounds is compelling, only the best companies will succeed. It takes tremendous rigor and excellent execution to steer through the complexities of drug development.?

As a healthcare investor myself, I will always bet on a phenomenal management team over simply a great idea. Cybin has consistently delivered on its clinical milestones, supported by what we believe is the strongest team in the sector, and we expect to continue to do so.?

We truly see a bright future for Cybin, and the potential to finally change the course of disease with these treatments, leading the way to transforming the mental health treatment landscape.

As always, we appreciate the continued support and commitment from our shareholders.

Thank you.